Study of the interaction between invariants "Natural Killer" T lymphocytes and Regulatory T cells in immunological diseases associated with the Th1/Th2 imbalance

• Grant number: 11/09868-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2011
• End date: January 31, 2015
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandre de Castro Keller
• Grantee: David Anibal Garrido Andrade
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Invariant "Natural Killer" T cells (NKT) represent a distinct subpopulation of T lymphocytes, and its main characteristics are selectivity for glycolipids and rapid secretion of a large number of pro and anti-inflammatory cytokines. Therefore, depending on the context in which NKT lymphocytes are activated, they can act both as effector or regulatory cells. On the other hand, the regulatory T lymphocytes (Treg) are key components for the preservation of immune homeostasis, playing an important role in the establishment and maintenance of immune tolerance to both self and non-self naturally harmless antigens, in order to avoid autoimmunity and hypersensivity reactions, respectively.Despite the importance of these two lymphocyte populations, the interaction between NKT cells and Treg cells is not well understood. There is evidence that NKT cells can promote proliferation of Treg lymphocytes, contributing to the control of immune responses, or exert cytotoxic activity on them, thereby participating in the pathogenesis of different diseases. On the other sense, there are studies showing that Treg cells can suppress both, proliferation and cytokine production by NKTcells.Another important issue is the recent identification of a NKT subset that expresses Foxp3pos cells and exerts suppressive activity. Considering that the works that focused on NKT cells did not consider the expression of Foxp3 and those that studied Tregs lymphocytes did not analyze the invariant TCR (present in NKT cells) it is possible that, on many models, populations named "regulatory cells" are a mix of infiltrating Tregs and NKTs.Therefore, in this project we will study the interaction NKT / Treg in three experimental models where the actions of these cells is crucial for the regulation of Th1/Th2 balance. In this vein, our proposal will contribute to the understanding of the processes involved in the modulation of the inflammatory diseases by regulatory cells. (AU)